Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Objective : To explore the causal relationship between 46 phenotypes ( including 15 seropositive case- control phenotypes and 31 quantitative antibody-measurement phenotypes) and ulcerative colitis( UC) using two- sample bidirectional Mendelian randomization( TSMR) . Methods: Single nucleotide polymorphisms ( SNPs) sig- nificantly associated with the relative abundance of the 46 antibody sera were extracted as instrumental variables ac- cording to preset thresholds . Summary statistics for UC were obtained from the OPEN GWAS database ( n = 47 745) . MR-Egger regression , weighted median method ( WME) , inverse variance weighting ( IVW) , the simple mode method (SM) , and weighted multitude method (WM) were used to estimate the causal relationship between antibody levels and UC , primarily using the IVW method . The results were assessed according to the effect indica- tor dominance ratios (OR) and 95% confidence intervals (CI) . Sensitivity analysis , heterogeneity test , gene plei- otropy test , and outlier test (MR-PRESSO) were combined to verify the stability and reliability of the results , and the causal association study was performed again using reverse Mendelian randomization(MR) . Results : IVW re- sults showed that Epstein-Barr( EB) virus EA-D antibody levels ( OR = 0. 806 , 95% CI = 0. 693 - 0. 939 , P < 0. 01) , Epstein-Barr virus EBNA-1 antibody levels ( OR = 1 . 870% , 95% CI = 1 . 480 - 2. 360 , P < 0. 000 1) , Anti-polyomavirus 2 IgG seropositivity (OR = 0. 570 , 95% CI = 0. 435 - 0. 746 , P < 0. 000 1) were associated with UC . The inverse MR analysis revealed a causal effect on anti-polyomavirus 2 IgG seropositivity , and none of the a- bove revealed genetic pleiotropy or significant heterogeneity of IVs . Conclusion EB virus EBNA-1 antibody levels are positively associated with the risk of UC , while EB virus EA-D antibody levels and anti-polyomavirus 2 IgG se- ropositivity are negatively associated with the risk of UC , indicating that they are protective factors for UC .

Objective To analyze the difference of rotator cuff muscle group fat content by MR proton density fat fraction(PDFF)tech-nology,and to explore the correlation between these variations and the severity grading of supraspinatus tendon injury.Methods Ninety-three patients with supraspinatus tendon injury were retrospectively selected and divided into the tendinitis group(grade Ⅰ),the partial tear group(grade Ⅱ),and the complete tear group(grade Ⅲ).The fat fraction(FF)values of the three groups of rotator cuff mus-cle group were measured using the PDFF technology,and the differences in FF values among the rotator cuff muscle group in the three groups were compared.The risk factors of the grading of supraspinatus tendon injury and the correlation between FF values and the severity grading of supraspinatus tendon injury were analyzed.Results The differences in the FF values of the supraspinatus and infraspinatus muscles among the three groups were statistically significant(P＜0.01).The FF values of both the supraspinatus and infraspinatus muscles were identified as significant factors associated with the severity grading of supraspinatus tendon injury.Further-more,the FF values of the supraspinatus and infraspinatus muscles were positively correlated with the severity grading of supraspina-tus tendon injury(r=0.576,P＜0.01;r=0.510,P＜0.01).Conclusion MR PDFF technology can effectively evaluate the extent of fat infiltration in the rotator cuff muscle group after supraspinatus tendon injury.Specifically,the FF values of the supraspinatus and infraspinatus muscles serve as reliable quantitative indicators for classifying supraspinatus tendon injury.

Objective To explore the impact of admission modes on the reperfusion time and short-term prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI).Methods 497 patients who visited the Chest Pain Center of Xiamen Cardiovascular Hospital of Xiamen University from January 2023 to November 2024 and were diagnosed with STEMI were included.All patients received direct percutaneous coronary intervention.According to admission modes,the patients were divided into the self-referral group(122 cases),emergency medical service group(EMS)(51 cases)and transfer PCI group(324 cases).The basic characteristics,reperfusion time,complications between group were compared.Results The age of the patients in this study was(58.64±13.62)years old,and there were 423 male cases(85.11%).Compared with the self-referral group and the EMS group,the time of door-wire in transfer PCI group was shorter[35(29,45)min vs.43(35,53)min vs.43(33,48)min,P＜0.001],but the time of first medical contact-wire was longer[123(80,192)min vs.43(35,52)min vs.57(51,76)min,P＜0.001].Compared with the self-referral group and the transfer PCI group,the time of symptom-to-first medical contact and the time of symptom-to-wire in EMS group were both shorter,which were[55(32,136)min vs.185(116,360)min vs.120(60,236)min,P＜0.001]and[136(101,188)min vs.228(169,413)min vs.282(190,400)min,P＜0.001].The incidence of infections in the transfer PCI group was lower than that in the self-referral group(12.65%vs.22.95%,P＜0.05).Conclusions To comprehensively enhance the treatment effect,it is necessary to prioritize the promotion and continuous optimization of the response process of EMS,simultaneously strengthen the standardized collaboration of referral,and enhance the identification ability of STEMI through public education to reduce the delay of self-referral patients..

Objective To analyze the difference of rotator cuff muscle group fat content by MR proton density fat fraction(PDFF)tech-nology,and to explore the correlation between these variations and the severity grading of supraspinatus tendon injury.Methods Ninety-three patients with supraspinatus tendon injury were retrospectively selected and divided into the tendinitis group(grade Ⅰ),the partial tear group(grade Ⅱ),and the complete tear group(grade Ⅲ).The fat fraction(FF)values of the three groups of rotator cuff mus-cle group were measured using the PDFF technology,and the differences in FF values among the rotator cuff muscle group in the three groups were compared.The risk factors of the grading of supraspinatus tendon injury and the correlation between FF values and the severity grading of supraspinatus tendon injury were analyzed.Results The differences in the FF values of the supraspinatus and infraspinatus muscles among the three groups were statistically significant(P＜0.01).The FF values of both the supraspinatus and infraspinatus muscles were identified as significant factors associated with the severity grading of supraspinatus tendon injury.Further-more,the FF values of the supraspinatus and infraspinatus muscles were positively correlated with the severity grading of supraspina-tus tendon injury(r=0.576,P＜0.01;r=0.510,P＜0.01).Conclusion MR PDFF technology can effectively evaluate the extent of fat infiltration in the rotator cuff muscle group after supraspinatus tendon injury.Specifically,the FF values of the supraspinatus and infraspinatus muscles serve as reliable quantitative indicators for classifying supraspinatus tendon injury.

Objective To explore the impact of admission modes on the reperfusion time and short-term prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI).Methods 497 patients who visited the Chest Pain Center of Xiamen Cardiovascular Hospital of Xiamen University from January 2023 to November 2024 and were diagnosed with STEMI were included.All patients received direct percutaneous coronary intervention.According to admission modes,the patients were divided into the self-referral group(122 cases),emergency medical service group(EMS)(51 cases)and transfer PCI group(324 cases).The basic characteristics,reperfusion time,complications between group were compared.Results The age of the patients in this study was(58.64±13.62)years old,and there were 423 male cases(85.11%).Compared with the self-referral group and the EMS group,the time of door-wire in transfer PCI group was shorter[35(29,45)min vs.43(35,53)min vs.43(33,48)min,P＜0.001],but the time of first medical contact-wire was longer[123(80,192)min vs.43(35,52)min vs.57(51,76)min,P＜0.001].Compared with the self-referral group and the transfer PCI group,the time of symptom-to-first medical contact and the time of symptom-to-wire in EMS group were both shorter,which were[55(32,136)min vs.185(116,360)min vs.120(60,236)min,P＜0.001]and[136(101,188)min vs.228(169,413)min vs.282(190,400)min,P＜0.001].The incidence of infections in the transfer PCI group was lower than that in the self-referral group(12.65%vs.22.95%,P＜0.05).Conclusions To comprehensively enhance the treatment effect,it is necessary to prioritize the promotion and continuous optimization of the response process of EMS,simultaneously strengthen the standardized collaboration of referral,and enhance the identification ability of STEMI through public education to reduce the delay of self-referral patients..

Objective:To investigate the influencing of preoperative total bilirubin (TBil) on perioperative complications of hepatolithiasis receiving liver resection.Methods:The retrospective cohort study was conducted. The clinical data of 300 patients with hepatolithiasis who were admitted to 2 medical centers from January 2010 to January 2022 were collected. There were 115 males and 185 females, aged (54±13)years. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for comparison between groups. Measurement data with skewed distribution were represented as M( Q1, Q3), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers, and the chi-square test was used for comparison between groups. Variables with P<0.10 in the univariate analysis were included into the multivariate analysis. Univariate analysis was conducted using the Logistic regression model,and multivariate analysis was conducted using the Logistic stepwise regression model with backward Wald method. Continuous variables were converted into categorical variables based on commonly reported cutoff values when conducting Logistic regression analysis. Results:(1) Comparison of clinical data of patients with different preoperative TBil. Of 300 patients with hepatolithiasis, there were 252 cases with low level of preoperative TBil as 14.4(11.1,19.7)μmol/L, and there were 48 cases with high level of preoperative TBil as 44.0(31.3,59.8)μmol/L. Of the pati-ents with low level of preoperative TBil, neutrophils percentage was 62%±10%, cases with intra-operative blood transfusion was 29, and cases undergoing anatomical liver resection was 166. Of the patients with high level of preoperative TBil, neutrophils percentage was 70%±11%, cases with intraoperative blood transfusion was 22, and cases undergoing anatomical liver resection was 15. There were significant differences in cases classified as>grade 2 of ASA classification, neutrophils percentage, cases with intraoperative blood transfusion and cases undergoing anatomical liver resection between patients with low and high level of preoperative TBil ( t=5.182, χ2=33.669, 18.775, P<0.05). (2) Comparison of perioperative complications of patients with different preoperative TBil. Of the 252 patients with low level of TBil, there were 151 cases with complications including 35 cases of serious complications, there was 1 case with postoperative liver failure, the duration of postoperative hospital stay was 13.0(10.0,16.0)days. Of the 48 patients with high level of TBil, there were 32 cases with complications including 17 cases of serious complications, there were 6 cases with postoperative liver failure, the duration of postoperative hospital stay was 14.0(10.0,18.8)days. There were significant differences in cases with serious complications and cases with postoperative liver failure between patients with low and high level of preoperative TBil ( χ2=13.041, 20.879, P<0.05). (3) Analysis of factors influencing postoperative serious complications in patients undergoing liver resection. Results of multivariate analysis showed that age, body mass index (BMI), preoperative TBil and volume of intraoperative blood loss were independent factors influencing postoperative serious complications in patients undergoing liver resection for hepatolithiasis ( odds ratio=3.852, 2.358, 2.935, 5.135, 95% confidence interval as 1.478?9.979, 1.110?5.009, 1.398?6.158, 2.088?12.626, P<0.05). Conclusions:Patients with high level of preoperative TBil have a significantly increased risk of postoperative serious complications and liver failure who receive liver resection for hepatolithiasis. Age, preoperative BMI, TBil and volume of intraoperative blood loss are independent factors influencing postoperative serious complications in patients undergoing liver resection for hepatolithiasis.

Objective To explore clinical effect of precast curvature internal fixation with Kirschner needle in treating forearm fracture in children.Methods From October 2019 to December 2022,32 children with forearm fractures were treated with precast curvature internal fixation with Kirkler's needles,including 25 males and 7 females,aged from 3 to 15 years old with an average of(8.0±0.5)years old,18 patients on the left side and 14 on the right side,24 patients with double fractures of radial and ulna,3 patients with Monteggia fractures,and 4 patients with Galeazzi fractures,and 1 patient with radial neck frac-ture of crooked cap.Operation time,intraoperative blood loss,C-arm fluoroscopy,fracture healing time and complications were recorded,and disabilities of arm,shoulder and hand(DASH)scale and Grace-Eversman forearm double fracture evaluation system were used to evaluate clinical efficacy of precast curvature internal fixation with Kirschner's needle for forearm fracture in children.Resluts All 32 patients were followed up for 2 to 12 months with an average of(7.16±2.51)months.Intraoperative blood loss was(20.68±5.50)ml,C-arm fluoroscopy was(5.80±2.50),and operation time was(24.34±5.10)min,fracture healing time was(8.82±1.62)weeks.Two patients occurred complications,including postoperative rupture of extensor pollicis longus tendon in 1 patient and obvious displacement of fracture caused by rotation of prefabricated curvature Kirschler needle on bone marrow cavity in 1 patient.DASH scores ranged from 0 to 16 scores with an average of(8.32±1.50)scores.According to Grace-Eversman double fracture evaluation system,28 patients got excellent result,2 good and 2 fair.Conclusion The treatment of forearm fracture with Kirschner's needle prefabricated curvature internal fixation has advantages of less trauma,less bleeding,good reduction,stable fixation,fast fracture healing and good functional recovery.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Objective:To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance.Method:Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups.Results:A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant ( χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups ( χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status ( t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment ( t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years ( t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points ( t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment ( t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing ( t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years ( t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE ( t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 ( t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion:Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.